The long-term objective of this program is to understand the mechanism(s) of fundamental cellular changes which occur during neoplastic transformation. Studies include: (a) growth, function or transformation of human, primate or mouse epithelial cells; (b) quantification of focal contact formation and association with cell shape changes and neoplastic transformation; and (c) studies on DNA-protein cross-link repair mechanism(s). The critical role of oxygen for sustained transepithelial transport by high density kidney epithelial cells was completed. Direct quantitative measure of oxygen consumption by kidney epithelial cells and nonneoplastic as well as tumorigenic keratinocytes revealed similar, rapid consumption rates irrespective of initial oxygen concentration, suggesting the cell population modifies the environment to minimize oxidation injury. In related studies, a vigorously proliferating, stable SV40 transformant of XP20S cells repairs DNA-protein cross-links almost as competently as normal skin fibroblasts, whereas untransformed XP20S cells retained most of the DNA-protein cross-link after an identical repair period. The data support the concept that continuous cell cycling compensates for the genetic deficiency in nucleotide excision repair by cells from xeroderma pigmentosum patients or is linked to an alternative repair pathway. Reflection-interference microscopy and computer-assisted morphometric analysis were used to quantify the area of focal contacts on the undersurface of normal and tumorigenic cells; the data show reduced spreading and cell shape change after transformation do not result from an impaired capacity to form focal contacts.